Developmental changes in cardiac contractility have been attributed to changes in cell structure and function. Our recent observation that the velocity of sarcomere shortening (S) is depressed in the isolated myocyte from the immature rabbit ventricle suggests that S can be used as a probe to explore the basis of developmental changes in contractility. We will test these hypotheses: 1) The developmental increase in S is due to developmental changes in the membrane systems that control activator calcium concentration; 2) S in the immature cell is primarily dependent on transsarcolemmal calcium movement during that contraction while S in the adult cell is primarily dependent on intracellular calcium stores; 3) The developmental acquisition of S dependency on intracellular stores is the result of developmental changes in the amount and orgainzation of the longitudinal, junctional and corbular sarcoplasmic reticulum (SR); 4) The quanitiative characteristics of the restitution of contractility between beats is related to the structure of the SR; 5) The developmental increase in sensitivity of the contractile apparatus to calcium; and 6) The physiologic differences between the rabbit and rat are a result of the corbular SR. At different stages of development, myocardial cells will be isolated from the rabbit and rat ventricle using enzymatic dispersion. Resting and action potentials will be measured. S in the intact cell will be measured in different calcium concentrations, (Ca)o, and contrasted to S or force obtained in the same cell, following detergent skinning. The isolated cell allows the beat-to-beat dependence of S on (Ca)o to be examined. (Ca)o will be changed transiently, e.g. increased during a contraction and then returned to control, and changes in S sought. The pattern of pacing will be altered in constant (Ca)o to discribe how S changes following a contraction. These variations in pacing will be performed also with step changes in (Ca)o. The effects on S of calcium channel blockers and ryanodine, which decreases the availability of calcium from internal stores, will be examined. Cell ultrastructure, e.g. the SR and the glycocalyx, will be examined with electron microscopy and related to the physiologic data. The comparison of the physiologic and ultrastructural properties at different stages of development will allow testing of the components of models of excitation-contraction coupling. By understanding the cellular basis for developmental changes in S, a better basis for therapeutic approaches to the sick child and infant can be established.